Mosquitoes are essential vectors for major human diseases such as malaria and dengue[unreadable] fever, which together infect hundreds of millions each year, killing millions. Current[unreadable] approaches to disease prevention, which include anti-pathogen drugs and vector suppression[unreadable] through the use of insecticides or environment modification, are insufficient.[unreadable] Replacement of wild mosquito populations with genetically modified counterparts that cannot[unreadable] transmit disease provides an alternative approach to disease prevention. However,[unreadable] mosquitoes carrying genes for disease refractoriness are not expected to have a higher[unreadable] fitness than native mosquitoes, and wild populations are large, dispersed over wide areas,[unreadable] and partially reproductively isolated. Thus, effective population replacement requires that[unreadable] genes conferring disease refractoriness be coupled with a genetic mechanism for driving[unreadable] these genes through the wild population at greater than Mendelian frequencies.[unreadable] We have developed a synthetic selfish genetic element (Medea) that can spread rapidly[unreadable] through a population, even if its presence or that of a linked cargo results in a fitness cost.[unreadable] Medea is the only selfish genetic element that has multiple features required for scientific and[unreadable] social acceptance of transgene release into the wild: the selfish genetic element and its cargo[unreadable] remain tightly linked; possibilities for horizontal spread within other species are limited;[unreadable] transgene recall from the wild and/or cycles of population replacement can be carried out.[unreadable] We will develop Medea and related drive mechanisms for several important mosquito vector[unreadable] species. This work will be carried out in collaboration with others who have developed[unreadable] transgenes conferring disease refractoriness and/or who can carry out cage trials to study[unreadable] selfish element/effector spread and efficacy in populations of uninfected and infected[unreadable] mosquitoes. My goal is to bring population replacement technology to the stage where it can[unreadable] be applied successfully, and the communities involved will have enough confidence the[unreadable] technology can be controlled to allow its use.